Context: Growth hormone (GH) replacement in PWS children has well defined benefits and risks and is used extensively worldwide. Its use in PWS adults has been limited by documentation of benefits and risks, as determined by larger multi-site studies.

Objectives: evaluate effectiveness and safety of GH in GH-deficient genotype positive PWS adults

Design: 12-month open label multicenter trial with 6-month dose-optimization and 6-month stable treatment periods

Setting: Outpatient treatment facilities at 4 US academic medical centers

Patients: Lean and obese PWS adults with diverse cognitive skills, behavioral traits, and living arrangements recruited from clinical populations

Intervention: Human recombinant GH (Genotropin®) initiated at 0.2mg/day with monthly 0.2mg increments to maximum 1.0mg/day, as tolerated

Main Outcomes Measures: LBM and %fat measured by DXA.

Results: LBM increased from 42.65([se]2.25]) to 45.47[2.31]kg (P.0001) and %fat decreased from 42.84[1.12] to 39.95[1.34] % (P = .025) at a median final dose of 0.6mg/day in 30 study subjects who completed 6–12 months of GH. Mean fasting glucose, 85.3[3.4]mg/dl, HbA1C 5.5[.2]%, fasting insulin 5.3[.6]µU/ml, AUC-insulin 60.4[7.5]µU/ml, HOMA-IR 1.1[.2] were normal at baseline in 38 study initiators, including 5 diabetics, and remained in normal range. Total T3 increased 26.7%: 127.0[7.8] to 150.5[7.8]ng/dl (P=.021) with normalization in all subjects, including 6(20%) with baseline T3's2 SD's below mean. Mildly progressive ankle edema was the most serious treatment emergent adverse event (5 patients).

Conclusions: This multi-center study demonstrates that GH improves body composition, normalizes T3, and is well tolerated without glucose impairment in PWS genotype adults.